fertility

Should we try Femara first?

letrozole-femara-fertility

For years clomiphene has been the main medication that fertility doctors and obgyns use to help women with polycystic ovarian syndrome and irregular cycles to get pregnant

That may be starting to change. In fertility practices such as ours, we have switched to a different drug, letrozole, also known by the brand name, Femara.

What is Letrozole?

Letrozole is a medication that blocks an enzyme in the body that converts testosterone into estrogen. It causes the estrogen levels to drop which lead to the pituitary gland to produce more of a hormone called FSH. FSH (follicle stimulating hormone) is the hormone the causes the eggs to start growing. By doing this, letrozole stimulates ovulation The most common use for letrozole is to help women with breast cancer reduce their risk of recurrence.

Why would you want to use letrozole instead of clomid?

Stimulation with letrozole results in fewer eggs than clomiphene, resulting in fewer multiple births. It is also less likely to cause the side effects of hot flashes and mood swings that are common with clomid.

So, what do the experts say about Femara?

The American College of Obstetrics and Gynecologists has endorsed letrozole as first line treatment for women with PCOS and infertility.

 

Acupuncture and Infertility

Acupuncture and IVF pregnancy rates: Princeton IVF blog
New study sheds doubt on whether acupuncture really helps IVF pregnancy rates

Lots of women seek out acupuncture to help them get pregnant, but does it really help?

Complementary and alternative medical treatments have become very popular for treating and preventing diseases, including the treatment of infertility. This may including vitamins and herbs and treatments such as acupuncture.

A number of researchers have found that acupuncture does improve fertility, at least in women who are undergoing IVF treatment, but some have not.

In order to figure out what it really going on, a group of doctors in Australia studies 824 women undergoing in vitro fertilization at their clinic. Half got real acupuncture (meaning the needles were placed in the right place according to acupuncture practice guidelines) and in the other half of patients, the needles were placed in locations that were not expected to have any effect. We call this last treatment "sham" acupuncture. They compared outcomes between the two groups.

They found out that women who had sham acupuncture were no more likely to get pregnant than those who had acupuncture done correctly. The pregnancy rates in these two groups were almost identical.

So what does this mean?

It is likely that acupuncture does not improve the chances for success with IVF, and if it does, the benefit is likely very small.

Were there any benefits to acupuncture in these women?

Yes. Women who received acupuncture were more relaxed and had a better sense of well being that those who had only sham acupuncture. This is not a small issue since IVF treatment is very stressful to the couples who are going through it.

Knowing this, should I still get acupuncture done?

Acupuncture is safe and comforting even if it may not be effective in IVF treatment. Other than the cost if it is not covered, there is really no risk to trying it.

Can menopause be reversed with stem cells?

Restoring fertility with stem cells: Princeton IVF blog
New research suggests bone marrow stem cells could be used restore estrogen and fertility in women with early menopause.

It may become possible in the near future

Women who suffer from premature menopause, also known as primary ovarian insufficiency (POI) or primary ovarian failure (POF) have either run out of eggs or no eggs capable of being stimulated.

This can occur for a number of reasons but early menopause causes 2 major problems for women who suffer from it. One is infertility, and this type of infertility can usually only be successfully treated with donor egg IVF. The other problem is hormonal. With the depletion of ovarian follicles, levels of reproductive hormones, especially estrogen, drop dramatically. The low levels of estrogen can cause a number of problems including vaginal dryness, difficulty with intercourse, hot flushes, bone loss and loss of sleep to name a few.

So, if there was a safe way to restore eggs to an ovary that has shut down prematurely, it might be a great advance in women's health care.

With that in mind, the ROSE trial was undertaken. The researchers injected cells from the bone marrow, which is rich in stem cells into the ovaries in an attempt to help regenerate new eggs.

Obtaining cells from the bone marrow is a fairly routine medical procedure and injecting substances into the ovarian is also not a new procedure. What is new about this is combining the two and using stem cell to restore ovarian function.

The few patients in the trial had an increase in the size of their ovaries and higher estrogen levels even a year out of from the procedure.

It will still take time and more studies to determine how safe and effective stem cells from the bone marrow are at restoring functioning ovaries and fertility to women with premature menopause / POI, but the results so far are encouraging. 

 

Your weight and your fertility

Your weight can affect your fertility: Princeton IVF blog
Being overweight can make it take longer to get pregnant in both men and women.

If either partner is overweight, it can harm your fertility

It has been know for for years that women who are overweight have a lower chance for success for IVF, and most fertility specialists encourage their patients who are overweight, to lose weight if possible, before treatment. So, the next logical questions is this: Does being overweight affect your chances of getting pregnant on your own even if you do not have infertility?

A study by National Institutes of Health (NIH) addressed that particular issue. The study was called the Longitudinal Investigation of Fertility and the Environment (LIFE) Study and they looked at couples who were both normal and with various degrees of being overweight to see how long it took them to conceive, commonly referred to as TTC. They looked about 500 couples from Texas and Michigan  and broke them down into 4 groups, normal weight (BMI 18-25), overweight (BMI 25-25), class I (BMI 30-34.9) and class II (BMI 35 and higher).  

The researchers found that in couples with class II obesity ( BMI > 35), it took 55% more time to conceive, than in normal weight couples.

It means that being significantly overweight not only affects your chances for pregnancy with fertility treatments such as IVF, it also makes it more difficult to conceive on your own.

The inventor of clomid and his legacy

The legacy of the inventor of clomiphene, Frank Palopali
Frank Palopali invented the fertility drug Clomid.

The story behind the first fertility drug, Clomid.

As the year draws to a close, the newspapers, TV stations and other media outlets will share stories about individuals whom we lost in the past year. We will hear stories about great artists, musicians, athletes, politicians and others, about how they lived their lives and how their life's work impacted our own lives. It is likely these accolades will miss out on someone whose impact on world of reproductive medicine and generations of couples suffering from infertility. That man was Frank Palopoli.

Who was Frank Palopali? 

Frank Palopali was a research chemist at the Merrell Dow Company. He was the leader of the team that developed clomiphene (Clomid) one of the most commonly used fertility drugs in the world. His work in the laboratory started back in the 1950's and first clinical trials of clomiphene were published in 1961. In 1967, Clomid was approved by the Food and Drug Administration and it became available to the public.

So, why was Clomid such a big deal? 

In this age of high tech, highly effective fertility treatments, IVF with genetic testing and the like, it is somewhat difficult to understand why an  inexpensive pill you pick up at Walmart for less than $10 might be such a big thing, but it was a huge breakthrough. If you look back to the world of women's reproductive health care 50 years ago, most fertility treatments were relatively ineffective and more often than not involved major surgery. For instance, the treatment of polycystic ovarian syndrome (PCOS) at the time involved in operation called the ovarian wedge resection. The gynecologic surgeon would make it open incision in the abdomen (similar to a cesarean section) and remove a wedge-shaped portion of the ovary, and then stitch the remaining ovary back together before closing the abdominal incision. Like other major surgeries, recovery from this operation could take weeks or months, but the benefit, if any, was very short term, just a few months afterwards. Additionally, eggs were inevitably lost in the process and scar tissue could develop on the surface of the ovaries, both of which could harm a woman's future fertility.

With the invention of clomiphene it was now possible to treat PCOS with just a pill. It completely revolutionized the treatment of infertility caused by problems of ovulation, and ovulation problems such as irregular cycles are among the most common causes of infertility in women. No longer would costly and invasive procedures be required, at least for most women with PCOS. While future inventions such as injectable fertility drugs, alternative methods of ovulation induction and IVF would bring success to many more people, it all started with the development of Clomid.

Over past nearly half a century since this time, millions upon millions of women all over the world have been able to have children and grow their families because of this invention. The number of couples helped by clomiphene actually dwarfs the number of those helped by IVF.

How does Clomiphene work?

Clomiphene is an anti-estrogen. It is part of a class of drugs called SERMs (selective estrogen receptor modulators) which include tamoxifen (Nolvadex) and reloxifene (Evista), drugs which are used to breast cancer and menopausal symptoms. Clomid works by blocking estrogen, the main female hormone. By blocking estrogen from working at the brain and pituitary gland (the master gland at the base of the brain), it tricks the body into sensing that there is no at there is no estrogen around. As a result, the hormones (FSH and LH) that stimulate the ovary, start to rise. This rise in hormones then kickstarts the process of the egg starting to grow and begins the path towards ovulation.

What are clomiphene's side effects?

It is easier to understand the side effects of clomiphene when you understand how it works. Because Clomid is anti-estrogen, it can cause hot flashes, headaches, breast discomfort and other symptoms that we normally associate with menopause. Because it stimulates the follicles (the cysts which contain the eggs) to grow, it can cause discomfort in the abdomen and increases the risk of multiple births. There are also concerns about whether clomiphene increases the risk of ovarian cancer, though most of the studies suggest it safe that when use for a brief period time. This is another reason to seek out the care of a fertility specialist early in the course of your treatment.

What is clomiphene used for?

The original and most common use for clomiphene is to help women who don't ovulate regularly, to produce and release eggs, become pregnant or hold on to a pregnancy. Clomiphene is also that used to help women produce multiple eggs to help improve the chances for success with insemination (IUI) and IVF. Clomiphene has also been used in men to assist in their fertility. This medication is intended to be used under the guidance of us physician experienced in their use.

How much is the price of clomiphene?

Like any other medication, the cost of clomiphene varies from pharmacy to pharmacy. Generic clomiphene in the typical starting dosing (50 mg) frequently sells for less than $10 at large retailers such as Walmart or Target. In the US, this medication always requires a prescription.

How many days after Clomid do you ovulate?

This a common question without a straight forward answer. Most women will ovulate around day 14 of the cycle, give or take a few days. Since clomiphene is usually taken day 3-7 or days 5-9, that means about 5-7 days after the last pill. However, some women will ovulate earlier, some later or not at all. At our center, we like to monitor everyone on clomiphene to make sure we get the timing right, and not delay pregnancy any longer than necessary.

Clomid success rate- how well does it work?

When used for to help infertile women with irregular or absent menstrual cycles, clomid enables about 80% of women to ovulate when used over a period of time. About half of these women will go on to conceive. This is actually quite good when you realize that natural conception in normal fertile women is only about 20-25%. The success rates when using clomiphene for other causes of infertility (unexplained, male infertility, endometriosis, etc.) is lower. 

Can clomiphene be used in men?

Clomid is sometimes used to treat male infertility, though it is considered an "off-label" use. Since its use and its effectiveness in men is somewhat more controversial than its use in women, it is best prescribed and managed by a urologist with special expertise in male fertility.

Celiac disease, fertility and pregnancy

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Is there a link between celiac disease, infertility and pregnancy complications?

Celiac disease is a relative common disorder of the gastrointestinal tract caused by an allergy to gluten, a protein commonly found in wheat and other grain products. Like many other diseases, it what we call an autoimmune disorder, a disease in which the body's immune system attacks the person's own normal cells. Treatment of this disease rarely requires any drugs and almost always is helped by changing one's diet to a gluten-free one. The disease is also known as celiac or nontropical sprue, or gluten-sensitive enteropathy. Women (and men) who suffer from celiac disease may have symptoms such as:

  • abdominal bloating and pain
  • diarrhea or constipation
  • weight loss
  • fatigue

Studies on Celiac disease have also reported higher rates of infertility, miscarriages and menstrual problems among women with the disease, and then once pregnant, higher rates of a number of pregnancy complications such as low birth weight babies. It has even been reported to affects male fertility.

So, does this mean the Celiac disease causes fertility and pregnancy problems? Not so fast. Many of these studies are really too weak and small to draw any real conclusions. Still other studies fail to show that Celiac disease causes any reproductive issues. At this time, issue is far from settled.

For those looking to find a reason for their otherwise unexplained infertility, this may not be for the answer. However, for those who are having trouble getting pregnant and have lots of gastrointestinal symptoms, it may not be a bad idea to ask your doctor about getting tested for Celiac disease.

 

Soy and fertility

Are soy products good or bad for your fertility?

soy-fertility.jpg

Soy products such as soy milk and tofu are high in protein and have become popular for their reported health benefits. So, why the concern?It turns out that soy products also contain chemicals called phytoestrogens. These phytoestrogens are chemicals found in plants that look and act like estrogens, the "female" sex hormones that both women and men produce naturally.  It is commonly believed (but not universally accepted) that these phytoestrogens may have health benefits such as reducing the risk of cardiovascular disease and taming the symptoms of menopause. One of the main concerns over the use of these "dietary supplements" is that if they act like estrogens, they may very well carry the the same risks as taking estrogen pills like Premarin and Estrace.

 So, how does this tie in with fertility issues? One of the key ingredients in birth control pills is a type of estrogen (commonly ethinyl estradiol) so it should come as no surprise there may that taking soy products could potentially be a problem for women attempting pregnancy.

With that in mind, researchers at Harvard's School of Public Health, looked at women undergoing IVF treatment to see if the use of soy products had any effect on the pregnancy rates. The results were somewhat surprising. IVF patients taking soy supplements were actually more likely to get pregnant. While the study was small and limited, and it is certainly to early to encourage women doing IVF to take in more soy products, it does appear to be reassuring for those trying to get pregnant and don't want to stop the soy milk and tofu.

Egg freezing- the controversy continues

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Egg freezing- Is it effective and is it a "fertility insurance?"

Several years back the American Society for Reproductive Medicine declared that the freezing and storage of unfertilized eggs (oocyte cryopreservation) was no longer experimental. Reproductive science specialists have worked out the kinks and figured how to freeze, thaw, fertilize and grow these eggs, and from them get healthy live born children. The initial focus was to help women who wanted to have children, but were facing cancer treatment (surgery, chemotherapy or radiation) that might render them sterile. The data on pregnancy rates was very sparse but it in comparison to the alternative in these women, moving forward was a no brainer.

Now researchers in in Canada, have published on the outcomes in couples based on US data. The pregnancy rates range from 4-12 %, and that is in young women under 30.  The rates are likely much lower in women in their 30s and 40s. While not great, it does offer some hope where there was none before. The problems is that now egg freezing is being used to delay childbearing in women for social reasons. With the announcement by google that they will pay for the procedure in their employees and the advent of "egg freezing parties," this is becoming more widespread.

As reproductive medicine specialists, we all want to offer our patients reproductive freedom, the ability to have children at a time that works out in their lives. Undoubtably, freezing and storing eggs for future use will enable some women to have children well into their 40's and early 50's. However, those who are unsuccessful with frozen eggs, and there will be many of them, will be left little choice other than using eggs from a donor, knowing that their biologic clock ran out while they had other priorities in life.

The problem is this: Is egg freezing an answer to a real problem? or is it giving women false hope? It may be a little of both. Only time will tell as the technology moves forward.